Polymer-immobilized alpha-iminoester

ABSTRACT

As an α-iminoester derivative that is stable under normal conditions and a method of producing various α-aminoester derivatives using them, a polymer-immobilized α-iminoester derivative represented by the following general formula (1)  
                 
 
     (wherein R 1  represents an alkyl chain of 1 or more carbons, and R 2  represents a hydrogen atom, halogen atom, or an alkyl group, aryl group or alkoxy group that may contain substituents), and a method of producing an α-iminoester derivative using them are provided.

TECHNICAL FIELD

[0001] The invention of the present application relates to apolymer-immobilized α-iminoester. More specifically, the invention ofthe present application relates to a method of producing an α-aminoesterderivative by using a polymer-immobilized α-iminoester.

BACKGROUND ART

[0002] The total synthesis of natural materials has become an importantsubject in various fields such as medicine, agricultural chemicals andperfumes. α-iminoesters are extremely useful as precursors ofnitrogen-containing natural compounds such as α-amino acids (J. Am.Chem. Soc., 1989, 111, 2582-2855; J. Org. Chem., 1988, 53, 1298-1307; J.Org. Chem., 1991, 56, 1894-1901) and β-amino alcohols (J. Org. Chem.,1976, 41, 3121-3124; J. Am. Chem. Soc., 1997, 119, 7871-7872), and haveattracted much attention. However, the monomer tends to decompose orpolymerize at room temperature and is extremely unstable and difficultto handle. For these reasons, α-amino acids had to be prepared justbefore use, making further progress in their use and developmentdifficult.

[0003] The present inventors have previously reported the immobilizationof unstable silyl enole ethers on resins and their use in variouscarbon-carbon bond forming reactions (Tetrahedron Lett., 1996, 37,2809-2812; Tetrahedron Lett., 1996, 37, 5569-5572; Tetrahedron Lett.,1996, 37, 7783-7736; Tetrahedron Lett., 1997, 38, 4251-4254; MoleculesOnline, 1998, 2, 35-39; J. Org. Chem. 1998, 63, 4868-4869). Ifanα-iminoester could be immobilized on a polymer in the same manner, thecompound maybe stabilized and its handling and storage may be madeeasier. However, because α-iminoesters are unstable on their own, asdescribed above, it was difficult to even introduce them to a polymer.

[0004] The invention of the present application has been accomplished inview of the aforementioned situations and its object is to provideα-iminoester derivatives that are stable under ordinary conditions andprovide a method of synthesizing various α-aminoester derivatives athigh yield using them, thereby overcoming the limitations of the priorart.

DISCLOSURE OF THE INVENTION

[0005] In order to accomplish the above-described objects, the inventionof the present application firstly provides a polymer-immobilizedα-iminoester represented by the following general formula (1):

[0006] (wherein R¹ represents an alkyl chain of more than 1 carbonatom(s), and R² represents a hydrogen atom, halogen atom, or an alkylgroup, aryl group or alkoxy group that may contain substituents.)

[0007] Further, the invention of the present application secondlyprovides a method of manufacturing an α-aminoester derivative,comprising the use of the above-described polymer-immobilizedα-iminoester.

BEST MODE FOR CARRYING OUT THE INVENTION

[0008] As described above, the invention of the present applicationcomprises the immobilization of an unstable α-iminoester on to apolymer, and hereinafter, the best mode for practicing the invention isdescribed in detail.

[0009] The polymer-immobilized α-iminoester represented by the generalformula (1) may be obtained by, for example, the hydrolysis ofcommercially available ethyldiethoxy acetate, followed by reaction witha chloromethylated resin and treatment of the resulting diethoxy acetateresin with a hydrochloric acid/dioxane solution, after which the activeintermediate is reacted with an amine.

[0010] In this process, R¹ of general formula (1) is an alkyl chain of 1or more carbon atoms. The length of the alkyl chain may vary dependingon the alkyl chain bonded to the phenyl group at the terminus of theresin (although said alkyl chain may also be omitted). Further, ahydrogen atom may be attached to the resin terminus instead of an alkylchain, in which case, R¹ becomes CH₂ by the chloromethylation of theresin terminus. Preferably, R¹ is an alkyl chain of 1 to 3 carbon atoms.

[0011] Further, in the above-described case, R² differs depending on theamine that is to be reacted; for example, an alkyl group such as methyl,ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, hexyl, cyclohexyl,cyclobutyl or cyclopentyl, an alkylene group such as ethylene,propylene, butylene or amylene, or an aryl group such as phenyl, toluylor xylyl may be applied. Further, these substituents may further containsubstituents. For example, halogenated phenyl group, benzyl group,o-methylphenyl group or p-methoxyphenyl group maybe considered.Preferable examples are p-methoxyphenyl, p-halogenated pheny; of course,R² is not restricted to these and may be selected according to thedesired α-aminoester derivative.

[0012] In the invention of the present application, α-amino acids can beobtained at high stereoselectivity and yield, by using the novelpolymer-immobilized α-iminoester of the present invention as a startingmaterial and reacting it with a nucleophile. Further,tetrahydroquinoline derivatives can be obtained at a high yield byreacting the above novel substance with various alkenes. Moreover, solidphase aza Diels-Alder reaction can be performed smoothly using thepolymer-immobilized α-iminoester of the present invention.

[0013] The structure of the nucleophile and the reactants such asalkenes are not particularly limited, and may be selected according tothe desired α-aminoester derivative species. Further, reactionconditions such as solvent, temperature and time, are not restrictedeither.

[0014] The invention of the present application is described morespecifically by the following Examples. It should be noted that thepresent invention is not restricted to these Examples.

EXAMPLE Reference Example 1 Synthesis of Polymer-Immobilizedα-Iminoester

[0015] A diacetoxy acetate resin was synthesized according to chemicalformula [A]. All products obtained after each step of the solid phasereaction were monitored by Swollen-Resin Magic Angle Spinning NMR(SR-MAS NMR).

[0016] (1) Synthesis of Diethoxyacetate Resin (Compound 2)

[0017] To a suspension of chloromethyl copoly(styrene-1%-divinylbenzene) resin (1.24 mmol/g, 10.0 g, 12.4 mmol) in DMF (100 ml), wasadded sodium diethoxyacetate (3.0 eq., 6.37 g, 37.2 mmol) andtetra-n-butyl ammonium iodide (1.0 eq., 4.58 g, 12.4 mmol), and stirredunder inert atmosphere for 12 hours at 60° C. After the reactionsolution was filtered and washed with water, THF and dichloromethane, adiethoxyacetate resin (Compound 2, 1.09 mmol/g) was obtained. Theloading of Compound (2) was determined by chlorine titration (Volhard'smethod). The result of identification was as shown in Table 1. TABLE 1Compound (2) ¹³C SR-MAS NMR (CDCl₃) δ = 15.0, 40.3, 62.3, 66.7, 97.3,125.6, 127.9, 145.3, 167.4 IR (KBr) 1755 cm⁻¹

[0018] (2) Synthesis of 2-Chloro-2-Ethoxyacetate Resin (Compound 3)

[0019] To a suspension of compound (2) (1.09 mmol/g, 10.0 g, 10.9 mmol)in 4N hydrogenchloride dioxane solution (100 ml) was added acetylchloride (5.0 eq., 3.9 ml, 54.5 mmol) and stirred at room temperaturefor 12 hours. After the reaction solution was filtered and washed withTHF and dichloromethane, a 2-chloro-2-ethoxyacetate resin (Compound 3,yield 99%, 1.10 mmol/g) was obtained. The loading of Compound (2) wasdetermined by chlorine titration (Volhard's method). The result ofidentification is shown in Table 2. TABLE 2 Compound (3) NMR (CDCl₃) δ =14.2, 40.3, 66.3, 67.7, 88.4, 125.6, 127.9, 145.3, 161.1 IR (KBr) 1760cm⁻¹

[0020] (3) Synthesis of 2-(4′-Methoxyphenyl)Iminoacetate Resin (Compound5)

[0021] To a suspension of compound (3) (1.10 mmol/g, 181.8 mg, 0.2 mmol)in DMF (100 ml) was added p-anisidine (Compound 4a) (5.0 eq., 123.2 mg,1.0 mmol) and stirred at room temperature for 12 hours. After thereaction solution was filtered and washed with THF and dichloromethane,a 2-(4′-methoxyphenyl) iminoacetate resin (Compound 5a, 1.10 mmol/g) wasobtained. The result of identification was as shown in Table 3. TABLE 3Compound (5a) NMR (CDCl₃) δ = 40.3, 55.4, 67.2, 114.5, 123.6, 125.6.127.9, 141.3, 147.5 160.5, 163.2 IR (KBr) 1760 cm⁻¹

[0022] (4) Conversion to 2-(4-methoxyphenyl)Aminoethanol (Compound 6a)

[0023] In order to determine the loading of the above-described Compound(5a), 2-(4′-methoxyphenyl)iminoacetate resin was transformed in to2-(4′-methoxyphenyl) aminoethanol (Compound 6a) by the followingprocedure.

[0024] Compound (5a) and lithium borane (5.0 eq., 21.8 mg, 1.0 mmol)were added to THF (5 ml) and stirred at room temperature for 12 hours.An aqueous 1N HCl solution was added to the reaction solution toterminate reaction, after which saturated sodium hydrogen carbonate wasadded. The aqueous layer was extracted with dichloromethane and theorganic layer was dried over sodium sulfate. After removing the solvent,the crude product was purified by TLC to obtain2-(4′-methoxyphenyl)aminoethanol (Compound 6a, 33.4 mg). The result ofidentification is shown below. TABLE 4 Compound (6a)¹HNMR(CDCl₃)δ=2.71(brs.2H), 3.25(t, 2H.J=5.2Hz), 3.75(s, 3H), 3.81(t,2H, J=5.2Hz), 6.63(d, 2H, J=9.0Hz), 6.79(d, 2H, J=9.0Hz):¹³CNMR(CDCl₃)δ=47.2, 55.8, 61.3, 114.5, 114.9, 142.2, 152.5:MS(EI)m/z=167 IR(KBr)1760cm⁻¹

[0025] Accordingly, identification results for 2-(4′-chlorophenyl)aminoethanol (6b) obtained by the above steps (3)-(4) using Compound 4bas the amine, and 2-(4′-bromophenyl)aminoethanol (6c) obtained by theabove steps (3)-(4) using 4c as the amine, are shown in Table 5 andTable 6, respectively. TABLE 5

Compound (6b) ¹H NMR (CDCl₃) δ = 2.69 (brs. 2H), 3.19 (t, 2H. J = 5.1Hz), 3.75 (t, 2H, J = 5.2 Hz), 6.50 (d, 2H, J = 8.9 Hz), 7.05 (d, 2H, J= 8.9 Hz): ¹³C NMR (CDCl₃) δ = 46.2. 61.1. 114.9, 122.5, 129.1, 146.6:MS (EI) m/z = 171

[0026] TABLE 6 Compound (6c) ¹HNMR(CDCl₃)δ=2.73(brs.2H), 3.20(t,2H.J=5.1Hz), 3.76(t, 2H, J=5.1Hz), 6.47(d, 2H, J=8.8Hz), 7.19(d, 2H,J=8.9Hz): ¹³CNMR(CDCl₃)δ=46.1, 61.1, 109.6, 114.8, 132.0, 146.9:MS(EI)m/z=215

Example 1 Mannich-Type Reaction Using Polymer-Immobilized α-Iminoester

[0027] A γ-oxo-α-amino acid derivative was synthesized by theMannich-type reaction using the polymer-immobilized α-iminoester of thepresent invention as the starting material in accordance with chemicalformula [B]

[0028] To a suspension of Sc(OTf)₃ (20 mol %, 19.7 mg, 0.04 mmol) andthe Compound (5a) (1.10 mmol/g, 181.8 mg. 0.2 mmol) indichloromethane-acetonitrile (1:1, 3 ml),1-methoxy-2-methyl-1-trimethylsiloxy-1-propene (Compound 7a, 5.0 eq.,174.3 mg, 1.0 mmol) in dichloromethane-acetonitrile (1:1, 1 ml) wasadded, and the mixture was stirred at room temperature for 20 hours.

[0029] After saturated aqueous sodium hydrogen carbonate was added toquench the reaction, the polymer was filtered and washed with water, THFand dichloromethane, and dried.

[0030] The resultant polymer was combined with sodium methoxide (2.0eq., 1M) in THF-methanol (1:1, 4 ml) and stirred for 1 hour at roomtemperature. After adding 4N HCl dioxane solution (0.1 ml), the reactionsolution was filtered and the solvents were removed from the filtrateunder a reduced pressure. The crude product was purified by preparativeTLC to afford dimethyl 3,3-dimethyl-2-(4′-methoxyphenyl)aminosuccinate(8a, 44.9 mg, yield 76%).

[0031] The identification result is shown below. TABLE 7 Compound (8a)¹HNMR(CDCl₃)δ=1.24(s, 3H), 1.28(s, 3H), 3.65(s, 3H), 3.69(s, 3H),3.71(s, 3H), 4.23(s, 1H), 6.67(d, 1H, J=8.8Hz), 6.74(d, 2H, J=8.8Hz):¹³CNMR(CDCl₃)δ=21.6, 22.5, 46.1, 52.0, 52.2, 55.7, 64.9, 114.8, 116.1,141.2, 153.2, 172.7, 176.1: IR(neat)1512, 1737, 3378cm⁻¹ MS(EI)m/z=295

[0032] Further, identification results for the products (Compound 8b-8c)obtained by the Mannich reaction of Compound (5a) with variousnucleophiles (Compounds 7b-7e) other than1-methyxo-2-methyl-1-polymethyl siloxy-1-propene (Compound 7a) shown inTable 8 are indicated in Tables 8 to 12. Particularly, whenDanishefsky's diene (J. Am. Chem. Soc., 1974, 96, 7807-7809; TetrahedronLett., 1982, 23, 3739-3742) was used as a nucleophile,2-methoxycarbonyl-1-(4′-methoxyphenyl)-1,2,3,4-tetrahydrop yridin-2-on(Compound 8e) was obtained in 69% yield. TABLE 8 (8a-d)

Yield Nucleophile Product (%)^(a)

76

94^(b)

71^(c)

65^(c,d)

69³

[0033] TABLE 9 Compound (8b) (major):¹HNMR(CDCl₃)δ=3.50(s, 3H), 3.64(s,3.H), 3.68(s, 3H), 4.37(d, 1H, J=11.9Hz), 4.41-4.53(m.2H), 4.61 (s, 1H),4.83(d, 1H, J=11.9Hz), 6.54(d, 2H, J=8.8Hz), 6.66 (d, 2H, J=8.8Hz),7.16-7.35(m, 5H):¹³CNMR(CDCl₃)δ=52.3, 52.4, 53.6, 60.8, 65.3, 73.0,114.6, 116.1, 128.1, 128.2, 128.4, 136.7, 140.6, 153.2, 170.2,171.1:(minor): ¹HNMR(CDCl₃)δ=3.658(s, 3H), 3.661(s, 3H), 3.73(s, 3H),4.27(d, 1H, J=3.7 Hz), 4.37(d, 1H,J =11.7Hz), 4.47)(d, 1H, J=3.7Hz),4.62(s, 1H), 4.76(d, 1H, J= 11.7Hz), 6.52(d, 2H, J=8.8Hz), 6.68(d, 2H,J=8.8Hz), 7.20-7.35(m, 5H):¹³C NMR(CDCl₃)δ=52.3, 52.5, 55.6, 60.3, 73.2,77.7, 114.9, 115.7, 127.9, 128.0, 128.4, 136.8, 139.4, 153.1, 170.3,170.5:IR(neat)1514, 1752, 3371cm⁻¹:MS(EI)m/z=373.

[0034] TABLE 10 Compound (8c) ¹HNMR(CDCl₃)δ=3.47(d, 2H, J=3.4Hz),3.65(s, 3H), 3.66(s, 3H), 4.48(t, 1H, J=5.4Hz). 6.60(d, 2H, J=8.9Hz),6.70(d, 2H, J=8.9Hz). 7.35-7.55(m, 3H), 7.80-7.90(m, 2H):¹³CNMR(CDCl₃)δ=41.1, 52.4, 54.2, 55.6, 114.8, 115.6, 128.1, 128.7,133.5, 136.3, 140.4, 153.0, 173.7, 197.3:IR(neat)1513, 1632, 1729,3365cm⁻¹:MS(EI)m/z=313.

[0035] TABLE 11 Compound (8d) ¹HNMR(CDCl₃)δ=1.22-1.36(m, 3H),3.58-3.65(m, 3H), 3.67-3.74(m, 3H), 3.92-4.06 (m, 1H), 4.32-4.41(m, 1H),6.49-6.77(m, 4H), 7.36-7.61 (m, 3H), 7.87(d, 2H, J=7.3Hz):¹³CNMR(CDCl₁)δ=13.6, 14.8, 43.2, 43.8, 52.0, 52.2, 55.6, 60.2, 61.0,114.7, 115.6, 115.8, 128.28, 128.30, 128.70, 128.73, 133.21, 133.29,135.9, 136.4, 140.6, 140.9, 152.9, 153.0, 173.4, 173.3, 201.3,201.8:IR(neat)1514, 1682, 1736, 3389cm⁻¹: MS(EI)m/z=261.

[0036] TABLE 12 Compound (8e) ¹HNMR(CDCl₃)δ=2.90(dq, 1H, J=1.1, 16.8Hz),3.05(dd, 1H, J=7.5, 16.8 Hz), 3.739(s, 3H), 3.78(s, 3H), 4.67(dd, 1H,J=1.1, 7.5Hz), 5.18(d, 1H, J=7.7Hz), 6.88(d, 2H, J=9.0Hz), 7.06(d, 2H,J=9.0Hz), 7.38(dd, 1H, J=1.1, 7.7Hz):¹³C NMR(CDCl₃)δ=38.3, 53.0, 55.5,61.1, 101.8, 114.7, 121.8, 138.1, 150.0, 157.3, 170.3,189.0:IR(neat)1509, 1581, 1652, 1743cm⁻¹:MS(EI)m/z=327.

Example 2 Synthesis of Tetrahydroquinoline Derivatives UsingPolymer-Immobilized α-Iminoester

[0037] Tetrahydroquinoline derivatives were synthesized according to thereaction of chemical formula [C].

[0038] To a suspension of Sc(OTf)₃ (20 mol %, 19.7 mg, 0.04 mmol) andCompound (5a) (1.10 mmol/g, 181.8 mg, 0.2 mmol) indichloromethane-acetonitrile (1:1, 3 ml), a solution of2,3-dihydropropane (Compound 9a, 5.0 eq., 70.1 mg, 1.0 mg, 1.0 mmol) indichloromethane-acetonitrile (1:1, 1 ml) was added and stirred at roomtemperature for 20 hours.

[0039] After the addition of saturated aqueous sodium hydrogen carbonateto quench the reaction, the resin was filtered and washed with water,THF and dichloromethane, and dried.

[0040] The resulting polymer and sodium methoxide (2.0 eq., 1M) wereadded to THF-methanol (1:1, 4 ml) and stirred at room temperature forone hour. After adding 4N HCl dioxane solution (0.1 ml), the reactionsolution was filtered and the solvent was removed under a reducedpressure. The crude product was purified by preparative TLC to obtain8-methoxy-4-methoxycarbonyl-2,3,3a,4,5,9b-hexahydrofurano [C]-quinoline(Compound 10a, 37.9 mg, yield 72%).

[0041] The identification result is shown in Table 13. TABLE 13 Compound(10a) ¹HNMR(CDCl₃)δ = 1.82-1.92(m, 1H), 1.95-2.06(m, 1H), 3.07(dq, 1H,J=3.2, 8.6Hz), 3.65-3.90(m, 7H), 4.44(d, 1H, J=3.2Hz), 5.15(d, 1H,J=8.6Hz), 6.56(d, 1H, J=8.6Hz), 6.69(dd, 1H, J=2.8, 8.6Hz), 6.84(d, 1H,J=2.8Hz): ¹³CNMR(CDCl₃)δ = 25.2, 40.3, 52.4, 55.7, 55.8, 66.6, 75.8,113.6, 115.9, 116.2, 123.1, 137.3, 153.2, 171.8; (minor): ¹³HNMR(CDCl₃)δ= 2.10-2.33(m, 2H), 2.60-2.69(m, 1H), 3.58(d, 1H, J=9.5Hz), 3.74(s, 3H),3.77-3.85(m, 4H), 3.92-4.00(m, 1H), 4.62(d, 1H, J=6.3Hz), 6.63 (d, 1H,J=8.8Hz), 6.73(dd, 1H, J=2.9, 8.8Hz), 6.89(d, 1H, J=2.9Hz):¹³CNMR(CDCl₃)δ = 29.6, 39.3, 52.4, 55.7, 56.2, 65.8, 75.1, 113.9, 116.5,116.6, 121.4, 136.9, 153.0, 172.8: IR(neat) 1622, 1737, 3367cm⁻¹.

[0042] Further, the same reaction was conducted using Compounds(5a)-(5c) as the starting material and Compounds (9a)-(9d) as thealkene. The resulting products, as well as their yield and selectivityare shown in the following table. TABLE 14 Materials TetrahydroquinolineDerivatives Yield Selectivity 5a + 9a

72%^(a) 68/32 5b + 9a

84%^(a) 60/32 5b + 9b

78%^(a) 75/25 5c + 9b

quant^(a) 68/32 5b + 9c

95%^(a) 95/5  5c + 9d

quant^(a) 93/7 

[0043] The identification results for Compounds (10b)-(10f) are shown inthe following Tables 15-19, TABLE 15 Compound (10b) (major):¹HNMR(CDCl₃)δ = 1.97-2.29(m, 2H), 2.53-2.60(m, 1H), 3.57(d, 1H,J=9.0Hz), 3.70-3.83(m, 4H), 3.89(dd, 1H, J=5.4, 8.4Hz), 4.53(d, 1H,J=6.1Hz), 6.54(d, 1H, J=8.7Hz), 6.99(dd, 1H, J=2.4, 8.7Hz), 7.23(d, 1H,J=2.4Hz): ¹³CNMR(CDCl₃)δ = 29.4, 38.8, 52.6, 55.3, 65.6, 116.2, 121.7,123.5, 128.9, 130.1, 141.6, 172.5: (minor): ¹HNMR(CDCl₃)δ = 1.70-2.00(m,2H), 2.95-3.10(m, 1H), 3.65-3.80(m, 5H), 4.14(d, 1H, J=3.1Hz), 5.07(d,1H, J=7.9Hz), 6.47(d, 1H, J=8.6 HZ), 6.95(dd, 1H, J=2.3, 8.6Hz), 7.20(d,1H, J=2.3Hz): ¹³CNMR(CDCl₃)δ = 25.0, 39.9, 52.6, 54.9, 66.6, 115.9,123.4, 123.8, 128.6, 129.5, 141.7, 172,5: IR (neat)1649, 1739cm⁻¹:MS(EI)m/z=267.

[0044] TABLE 16 Compound (10c) (major): ¹HNMR(CDCl₃)δ = 1.64(s, 3H),2.15(dd, 1HJ=4.1, 13.4Hz), 2.24(dd, 1H, J=10.1, 13.4Hz), 3.53(s, 3H),4.10(dd, 1H, J=4.1, 10.1Hz), 6.53(d, 1H, J=8.5Hz), 6.60(d, 1H, J=2.4Hz),6.90 (dd, 1H, J=2.4, 8.5Hz), 7.11-7.25(m, 5H): ¹³CNMR(CDCl₃)δ = 28.7,41.20, 41.23, 51.4, 52.3, 115.9, 122.2, 126.4, 127.2, 127.3, 128.1,128.6, 130.3, 141.2, 148.0, 173.2: (minor): ¹HNMR(CDCl₃)δ = 1.67(s, 3H),1.87(dd, 1HJ=12.3, 12.9Hz), 2.43(dd, 1H, J=3.5, 12.9Hz), 3.52(dd, 1H,J=3.5, (2.3Hz), 3.66(s, 3H), 6.33(d, 1H, J=9.0Hz), 6.95-7.32(m, 5H):¹³CNMR(CDCl₃)δ = 29.0, 40.1, 41.1, 50.8, 52.4, 114.6, 115.6, 126.3,126.9, 127.4, 127.6, 128.4, 129.1, 141.5, 147.9, 173.4: IR(neat)1713,3384cm⁻¹: MS(EI)m/z=315.

[0045] TABLE 17 Compound (10d) (major): ¹HNMR(CDCl₃)δ = 1.71(s, 3H),2.21(dd, 1HJ=4.1, 13.3Hz), 2.30(dd, 1H, J=10.1, 13.3Hz), 3.59(s, 3H),4.16(dd, 1H, J=4.1, 10.1Hz), 6.54(d, 1H, J=8.6Hz), 6.80(d, 1H, J=2.1Hz),7.10 (dd, 1H, J=2.1, 8.6Hz), 7.15-7.40(m, 5H): ¹³CNMR(CDCl₃)δ = 28.7,41.2, 51.4, 52.3, 100.5, 109.3, 116.3, 126.4, 127.3, 128.2, 128.9,130.0, 130.7, 131.45, 131.51, 132.2, 141.6, 147.9, 173.1: (minor):¹HNMR(CDCl₃)δ = 1.75(s, 3H), 1.94(dd, 1HJ=12.2, 12.8Hz), 2.50(dd, 1H,J=3.4, 12.8Hz), 3.59(dd, 1H, J=3.4, 12.8Hz), 3.73(s, 3H), 6.55(d, 1H,J=8.6Hz), 7.06(d, 2H, J=7.2Hz), 7.18(dd, 1H, J=2.0, 6.4Hz), 7.30-7.43(m,3H): ¹³CNMR(CDCl₃)δ = 29.0, 40.1, 41.1, 50.8, 52.4, 109.1, 116.0, 126.3,126.9, 128.2, 128.4, 130.2, 130.5, 141.9, 147.9, 173.4: IR(neat)1713,3408cm⁻¹: MS(EI)m/z=359.

[0046] TABLE 18 Compound (10e) ¹HNMR(CDCl₃)δ = 2.68(dd, 1H, J=8.0,15.4Hz), 3.02(dd, 1H, J=10.2, 15.4Hz), 3.29-3.39(m, 1H), 3.71(s, 3H),4.10,(d, 1H, J=3.2Hz), 4.33(d, 1H, J=8.3Hz), 6.42(d, 1H, J=8.6Hz),6.80(dd, 1H, J=2.2, 8.6Hz), 7.00-7.15(m, 3H): ¹³CNMR(CDCl₃)δ = 31.6,42.3, 45.5, 52.3, 116.5, 123.2, 124.8, 124.9, 125.1, 126.7, 126.8,127.3, 128.7, 141.8, 142.1, 144.9, 171.9: IR(neat)1713, 3409cm⁻¹:MS(EI)m/z=313.

[0047] TABLE 19 Compound (10f) ¹HNMR(CDCl₃)δ = 1.75(s, 3H), 2.58-2.70(m,1H), 2.90-3.02(m, 2H), 3.85(s, 3H), 4.31(d, 1H, J=2.4Hz)6.45(d, 1H,J=8.8Hz), 6.99(dd, 1H, J=2.4, 8.8Hz), 7.080-7.30(m, 4H), 7.48(d, 1H,J=7.2Hz): ¹³CNMR(CDCl₃)δ = 29.6, 30.6, 48.1, 49.7, 52.1, 52.5, 110.0,116.6, 123.4, 124.8, 126.8, 127.2, 128.8, 129.7, 131.5, 140.7, 141.0,148.7, 172.4: IR(neat)1712, 3409cm⁻¹: MS(EI)m/z=371.

[0048] In each of the reactions, the solid phase reaction proceededsmoothly and tetrahydroquinoline derivatives corresponding to eachstarting material and reactant were obtained at high yield. Further, itwas shown that even halogenated compounds were stable in thesereactions.

INDUSTRIAL APPLICABILITY

[0049] As has been described above in detail, a new polymer-immobilizedα-iminoester has been provided by the invention of the presentapplication. Using this polymer-immobilized α-iminoester, α-aminoesterderivatives, which are known to be important in the field ofbiochemistry, can be synthesized in high yield.

1. A polymer-immobilized α-iminoester, which is represented by thefollowing general formula (1):

(wherein R¹ represents an alkyl chain of 1 or more carbon atom(s), andR² represents a hydrogen atom, halogen atom, or an alkyl group, arylgroup or alkoxy group that may contain substituents).
 2. A method ofproducing an α-aminoester derivative comprising the use of thepolymer-immobilized α-iminoester of claim 1.